Before initiating treatment with abacavir-containing products, HLA-B*5701 status must always be documented. Abacavir should not be used in patients known to carry the HLA-B*5701 allele due to the risk of hypersensitivity reaction.

Indication and Dosing

TRIUMEQ is indicated for the treatment of HIV-infected adults and adolescents above 12 years of age weighing at least 40 kg.

Before initiating treatment with abacavir-containing products, HLA-B*5701 status must always be documented. Abacavir should not be used in patients known to carry the HLA-B*5701 allele due to the risk of hypersensitivity reaction.

†TRIUMEQ is a fixed-dose pill and should not be prescribed for patients requiring dose adjustments. Separate preparations of dolutegravir, abacavir, and lamivudine are available in cases where discontinuation or dose adjustment is required.

‡TRIUMEQ is not recommended for patients with integrase inhibitor resistance.

§TRIUMEQ is not recommended for co-administration with efavirenz, nevirapine, rifampicin, or tipranavir/ritonavir

Since the recommended dose of dolutegravir is 50 mg twice daily for patients taking etravirine without boosted protease inhibitors, Triumeq is not recommended for patients taking etravirine without co-administration of atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir (see further below in table).

Lopinavir + Ritonavir +
Etravirine/
Dolutegravir

Dolutegravir ↔

AUC ↑ 11 %

Cmax ↑ 7 %

Cτ ↑ 28 %

Lopinavir ↔

Ritonavir ↔

Etravirin ↔

No dose adjustment is necessary.

Darunavir + Ritonavir +
Etravirine/
Dolutegravir

Dolutegravir ↓

AUC ↓ 25 %

Cmax ↓ 12 %

Cτ ↓ 36 %

Darunavir ↔

Ritonavir ↔

Etravirine ↔

No dose adjustment is necessary.

Efavirenz/Dolutegravir

Dolutegravir ↓

AUC ↓ 57 %

Cmax ↓ 39 %

Cτ ↓ 75 %

Efavirenz ↔ (historical controls)

(induction of UGT1A1 and CYP3A enzymes)

Since the dose of dolutegravir is 50 mg twice daily when co-administered with efavirenz, the co-administration of efavirenz with Triumeq is not recommended.

Nevirapine/Dolutegravir

Dolutegravir ↓

(Not studied, a similar reduction in exposure as observed with efavirenz is expected, due to induction)

Co-administration with nevirapine may decrease dolutegravir plasma concentration due to enzyme induction and has not been studied.

Effect of nevirapine on dolutegravir exposure is likely similar to or less than that of efavirenz.

Since the dose of dolutegravir is 50 mg twice daily when co-administered with nevirapine, the co-administration of nevirapine with Triumeq is not recommended.

Rilpivirine

Dolutegravir ↔

AUC ↑ 12 %

Cmax ↑ 13 %

Cτ ↑ 22 %

Rilpivirine ↔

No dose adjustment is necessary.

HIV-1 Antiviral Agents

NRTI

Medical Products by therapeutic areas

Interaction

Geometric mean change (%)

Recommendations concerning co-administration

Tenofovir

Emtricitabine, didanosine,stavudine, zidovudine.

Dolutegravir ↔

AUC ↑ 1 %

Cmax ↓ 3 %

Cτ ↓ 8 %

Tenofovir ↔

Interaction not studied

No dose adjustment is necessary when Triumeq is combined with nucleoside reverse transcript inhibitors.

Triumeq is not recommended for use in combination with emtricitabine containing products, since both lamivudine (in Triumeq) and emtricitabine are cytidine analogues (i.e. risk for intracellular interactions).

HIV-1 Antiviral Agents

Protease Inhibitors

Medical Products by therapeutic areas

Interaction

Geometric mean change (%)

Recommendations concerning co-administration

Atazanavir/Dolutegravir

Dolutegravir ↑

AUC ↑ 91 %

Cmax ↑ 50 %

Cτ ↑ 180 %

Atazanavir ↔ (historical controls)

(inhibition of UGT1A1 and CYP3A enzymes)

No dose adjustment is necessary.

Atazanavir + Ritonavir/
Dolutegravir

Dolutegravir ↑

AUC ↑ 62 %

Cmax ↑ 34 %

Cτ ↑ 121 %

Atazanavir ↔

Ritonavir ↔

No dose adjustment is necessary.

Tipranavir + Ritonavir/
Dolutegravir

Dolutegravir ↓

AUC ↓ 59 %

Cmax ↓ 47 %

Cτ ↓ 76 %

Tipranavir ↔

Ritonavir ↔

(induction of UGT1A1 and CYP3A enzymes)

Since the recommended dose of dolutegravir is 50 mg twice daily when co-administered with tipranavir/ritonavir, the co-administration of tipranavir/ritonavir with Triumeq is not recommended.

Fosamprenavir + Ritonavir/
Dolutegravir

Dolutegravir ↓

AUC ↓ 35 %

Cmax ↓ 24 %

Cτ ↓ 49 %

Fosamprenavir ↔

Ritonavir ↔

(induction of UGT1A1 and CYP3A enzymes)

Fosamprenavir/ritonavir decreases dolutegravir concentrations, but based on limited data, did not result in decreased efficacy in Phase III studies.

No dose adjustment is necessary.

Nelfinavir/Dolutegravir

Dolutegravir ↔

(Not studied)

No dose adjustment is necessary.

Lopinavir + Ritonavir/
Dolutegravir

Dolutegravir ↔

AUC ↓ 4 %

Cmax↔ 0 %

C24 ↓ 6 %

Lopinavir ↔

Ritonavir ↔

No dose adjustment is necessary.

Darunavir + Ritonavir/
Dolutegravir

Dolutegravir ↓

AUC ↓ 22 %

Cmax ↓ 11 %

Cτ ↓ 38 %

Darunavir ↔

Ritonavir ↔

(induction of UGT1A1 and CYP3A enzymes)

No dose adjustment is necessary.

Other Antiviral Agents

Medical Products by therapeutic areas

Interaction

Geometric mean change (%)

Recommendations concerning co-administration

Telaprevir / Dolutegravir + Abacavir + Lamivudine

Dolutegravir ↑

AUC ↑ 25 %

Cmax ↑ 19 %

Cτ ↑ 37 %

Telaprevir ↔ (historical controls)

(inhibition of CYP3A enzyme)

Interaction with abacavir not studied

Interaction with lamivudine not studied

No dose adjustment is necessary with dolutegravir.

Based on metabolism and clearance of abacavir a clinically significant interaction is unlikely.

Based on metabolism and clearance of lamivudine a clinically significant interaction is unlikely.

Boceprevir / Dolutegravir + Abacavir + Lamivudine

Dolutegravir ↔

AUC ↑ 7 %

Cmax ↑ 5 %

Cτ ↑ 8 %

Boceprevir ↔ (historical controls)

Interaction with abacavir not studied

Interaction with lamivudine not studied

No dose adjustment is necessary with dolutegravir.

Based on metabolism and clearance of abacavir a clinically significant interaction is unlikely.

Based on metabolism and clearance of lamivudine a clinically significant interaction is unlikely.

Daclatasvir / Dolutegravir + Abacavir + Lamivudine

Dolutegravir ↔

AUC ↑ 33 %

Cmax ↑ 29 %

Cτ ↑ 45 %

Daclatasvir ↔

Interaction with abacavir not studied

Interaction with lamivudine not studied

Daclatasvir did not change dolutegravir plasma concentration to a clinically relevant extent.

Based on abacavir and lamivudine metabolism and clearance a clinically significant interaction is unlikely.

Please see the Liverpool Drug-Drug Interaction Table for further information.

Elbasvir / Grazoprevir / Dolutegravir + Abacavir + Lamivudine

AUC ↑ 16%

CmaxÂ ↑ 22%

Ctrough 14%

Interaction with abacavir not studied

Interaction with lamivudine not studied

Coadministration of multiple doses of elbasvir / grazoprevir and dolutegravir had no clinically significant effect on the pharmacokinetics of grazoprevir, elbasvir or dolutegravir. No dose adjustments are required. (In 12 subjects). No clinically significant interaction expected.

Based on abacavir and lamivudine metabolism and clearance a clinically significant interaction is unlikely.

Triumeq and dofetilide co-administration is contraindicated due to potential life-threatening toxicity caused by high dofetilide concentration.

Medical Products by therapeutic areas

Interaction

Geometric mean change (%)

Recommendations concerning co-administration

Magnesium/aluminium-containing antacids/Dolutegravir

Dolutegravir ↓

AUC ↓ 74 %

Cmax ↓ 72 %

(Complex binding to polyvalent ions)

Magnesium/ aluminium-containing antacids should be taken well separated in time from the administration of Triumeq (minimum 2 hours after or 6 hours before).

Calcium supplements/
Dolutegravir

Dolutegravir ↓

AUC ↓ 39 %

Cmax ↓ 37 %

C24 ↓ 39 %

(Complex binding to polyvalent ions)

Calcium supplements, iron supplements or multivitamins should be taken well separated in time from the administration of Triumeq (minimum 2 hours after or 6 hours before).

Iron supplements/
Dolutegravir

Dolutegravir ↓

AUC ↓ 54 %

Cmax ↓ 57 %

C24 ↓ 56 %

(Complex binding to polyvalent ions)

Multivitamins/Dolutegravir

Dolutegravir ↓

AUC ↓ 33 %

Cmax ↓ 35 %

C24 ↓ 32 %

Medical Products by therapeutic areas

Interaction

Geometric mean change (%)

Recommendations concerning co-administration

Prednisone

Dolutegravir ↔

AUC ↑ 11 %

Cmax ↑ 6 %

Cτ ↑ 17 %

No dose adjustment is necessary.

Medical Products by therapeutic areas

Interaction

Geometric mean change (%)

Recommendations concerning co-administration

Metformin/Dolutegravir

Metformin ↑

Dolutegravir ↔

When co-administered with dolutegravir 50mg QD: Metformin

AUC ↑ 79 %

Cmax ↑ 66 %

When co-administered with dolutegravir 50mg BID: Metformin

AUC ↑ 145 %

Cmax ↑ 111 %

A dose adjustment of metformin should be considered when starting and stopping coadministration of dolutegravir with metformin, to maintain glycaemic control.

In patients with moderate renal impairment a dose adjustment of metformin should be considered when coadministered with dolutegravir, because of the increased risk for lactic acidosis in patients with moderate renal impairment due to increased metformin concentration.

Medical Products by therapeutic areas

Interaction

Geometric mean change (%)

Recommendations concerning co-administration

St. John's wort/Dolutegravir

Dolutegravir ↓

(Not studied, decrease expected due to induction of UGT1A1 and CYP3A enzymes, a similar reduction in exposure as observed with carbamazepine is expected)

Since the recommended dose of dolutegravir is 50 mg twice daily when co-administered with St. John's wort, DTG/ABC/3TC FDC is not recommended.